Effects of asfotase alfa in adults with pediatric-onset hypophosphatasia over 24months of treatment.

Abstract

Hypophosphatasia (HPP) is a rare, heritable metabolic disorder caused by deficient activity of tissue-nonspecific alkaline phosphatase (TNSALP). Asfotase alfa (AA) is a human recombinant TNSALP that promotes bone mineralization and is approved to treat eligible patients with HPP. This prospective single-center observational study evaluated AA in adults with pediatric-onset HPP over 2years of treatment (ClinicalTrials.govNCT03418389). Primary outcomes evaluated physical function; secondary outcomes assessed quality of life (QoL) and pain. The study included 17 females and 5 males (mean age: 48.7years). Median distance walked in the 6-Minute Walk Test increased significantly from baseline to 12months (P=0.034) and results were sustained. Median Timed Up and Go test time significantly decreased from baseline at 12 (P=0.003) and 24months (P=0.005), as did the median chair rise time test at 12 (P=0.003) and 24months (P<0.002). The change from baseline in usual gait speed was significant at 12 (P=0.003) and 24months (P=0.015). Mean dominant and nondominant hand grip strength improved at 24months (P=0.029 and P=0.019, respectively). Median Short Form 36 Physical Component Summary scores significantly improved from baseline at 12 (P=0.012) and 24 (P=0.005) months, and median Lower Extremity Functional Scale scores improved from baseline at 12 (P=0.001) and 24 (P=0.002) months. No significant change was noted in pain level at these timepoints. While injection site reactions occurred in 86.4% of the participants, there were no severe side effects or safety findings. Adults with pediatric-onset HPP treated with AA experienced marked improvement in functional and QoL outcomes that were observed as early as within 3months of initial treatment and were sustained over 24months.